White-Matter Hyperintensities and Lacunar Infarcts Are Associated with an Increased Risk of Alzheimer’s Disease in the Elderly in China

Shuai Ye,Shuyang Dong,Jun Tan,Le Chen,Hai Yang,Yang Chen,Zeyan Peng,Yingchao Huo,Juan Liu,Mingshan Tang,Yafei Li,Huadong Zhou,Yong Tao 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.1

Background and Purpose This study investigated the contribution of white-matter hyperintensities (WMH) and lacunar infarcts (LI) to the risk of Alzheimer’s disease (AD) in an elderly cohort in China. Methods Older adults who were initially cognitively normal were examined with MRI at baseline, and followed for 5 years. WMH were classified as mild, moderate, or severe, and LI were classified into a few LI (1 to 3) or many LI (≥4). Cognitive function was assessed using the Mini Mental State Examination and the Activities of Daily Living scale. Results Among the 2,626 subjects, 357 developed AD by the end of the 5-year follow-up period. After adjusting for age and other potential confounders, having only WMH, having only LI, and having both WMH and LI were associated with an increased risk of developing AD compared with having neither WMH nor LI. Moderate and severe WMH were associated with an increased risk of developing AD compared with no WMH. Furthermore, patients with many LI had an increased risk of developing AD compared with no LI. Conclusions Having moderate or severe WMH and many LI were associated with an increased risk of developing AD, with this being particularly striking when both WMH and LI were present.

Inhibition of MicroRNA-15a/16 Expression Alleviates Neuropathic Pain Development through Upregulation of G Protein-Coupled Receptor Kinase 2

( Tao Li ),( Yingchun Wan ),( Lijuan Sun ),( Shoujun Tao ),( Peng Chen ),( Caihua Liu ),( Ke Wang ),( Changyu Zhou ),( Guoqing Zhao ) 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.4

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-1β and tumor-necrosis factor-αin the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and NF-κB in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.

Clinicopathologic Characteristics and Prognoses for Multicentric Occurrence and Intrahepatic Metastasis in Synchronous Multinodular Hepatocellular Carcinoma Patients

Li, Shi-Lai,Su, Ming,Peng, Tao,Xiao, Kai-Yin,Shang, Li-Ming,Xu, Bang-Hao,Su, Zhi-Xiong,Ye, Xin-Ping,Peng, Ning,Qin, Quan-Lin,Chen, De-Feng,Chen, Jie,Li, Le-Qun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the outcomes for patients are still poor. It is important to determine the original type of synchronous multinodular HCC for preoperative assessment and the choice of treatment therapy as well as for the prediction of prognosis after treatment. Aims: To analyze clinicopathologic characteristics and prognoses in patients with multicentric occurrence (MO) and intrahepatic metastasis (IM) of synchronous multinodular hepatocellular carcinoma (HCC). Methods: The study group comprised 42 multinodular HCC patients with a total of 112 nodules. The control group comprised 20 HCC patients with 16 single nodular HCC cases and 4 HCC cases with a portal vein tumor emboli. The mitochondrial DNA (mtDNA) D-loop region was sequenced, and the patients of the study group were categorized as MO or IM based on the sequence variations. Univariate and multivariate analyses were used to determine the important clinicopathologic characteristics in the two groups. Results: In the study group, 20 cases were categorized as MO, and 22 as IM, whereas all 20 cases in the control group were characterized as IM. Several factors significantly differed between the IM and MO patients, including hepatitis B e antigen (HBeAg), cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and the histological grade of the primary nodule. Multivariate analysis further demonstrated that cirrhosis and portal vein and/or microvascular tumor thrombus were independent factors differentiating between IM and MO patients. The tumor-free survival time of the MO subjects was significantly longer than that of the IM subjects ($25.7{\pm}4.8$ months vs. $8.9{\pm}3.1$ months, p=0.017). Similarly, the overall survival time of the MO subjects was longer ($31.6{\pm}5.3$ months vs. $15.4{\pm}3.4$ months, p=0.024). The multivariate analysis further demonstrated that the original type (p=0.035) and Child-Pugh grade (p<0.001) were independent predictors of tumor-free survival time. Cirrhosis (p=0.011), original type (p=0.034) and Child-Pugh grade (p<0.001) were independent predictors of overall survival time. Conclusions: HBeAg, cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and histological grade of the primary nodule are important factors for differentiating IM and MO. MO HCC patients might have a favorable outcome compared with IM patients.

Bicluster and Pathway Enrichment Analysis of HCV-induced Cirrhosis and Hepatocellular Carcinoma

Cheng, Peng,Cheng, You,Su, Mei X.,Li, Dong,Zhao, Guo Z.,Gao, Hui,Li, Yan,Zhu, Jie Y.,Li, Hua,Zhang, Tao Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the most common form of liver cancer. However, while it is associated frequently with hepatitis C virus (HCV) there is only an elementary understanding of its molecular pathogenesis. Methods: To gain insight into the molecular mechanisms of HCV-induced hepatocarcinogenesis, we performed microarray analysis on 75 surgical liver samples from 48 HCV-infected patients. Results: There were 395 differentially expressed geness between cirrhotic samples and HCC samples. Of these, 125 genes were up-regulated and 270 genes were down-regulated. We performed pathway enrichment analysis and screened as described previously. Conclusions: The differentially expressed genes might be involved in hepatocarcinogenesis through upregulating the pathways of ECM-receptor interaction, focal adhesion, cell adhesion molecules and other cancer-related pathways, and downregulating the pathways of "complement and coagulation cascades". We hope our results could aid in seeking of therapeutic targets for HCV-induced hepatocellular carcinoma.

Comparison of the Gene Expression Profiles Between Smokers With and Without Lung Cancer Using RNA-Seq

Cheng, Peng,Cheng, You,Li, Yan,Zhao, Zhenguo,Gao, Hui,Li, Dong,Li, Hua,Zhang, Tao Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Lung cancer seriously threatens human health, so it is important to investigate gene expression changes in affected individuals in comparison with healthy people. Here we compared the gene expression profiles between smokers with and without lung cancer. We found that the majority of the expressed genes (threshold was set as 0.1 RPKM) were the same in the two samples, with a small portion of the remainder being unique to smokers with and without lung cancer. Expression distribution patterns showed that most of the genes in smokers with and without lung cancer are expressed at low or moderate levels. We also found that the expression levels of the genes in smokers with lung cancer were lower than in smokers without lung cancer in general. Then we detected 27 differentially expressed genes in smokers with versus without lung cancer, and these differentially expressed genes were foudn to be involved in diverse processes. Our study provided detail expression profiles and expression changes between smokers with and without lung cancer.

Association of DNA Base-excision Repair XRCC1, OGG1 and APE1 Gene Polymorphisms with Nasopharyngeal Carcinoma Susceptibility in a Chinese Population

Li, Qing,Wang, Jian-Min,Peng, Yu,Zhang, Shi-Heng,Ren, Tao,Luo, Hao,Cheng, Yi,Wang, Dong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

Background: Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles. Aims: To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma. Materials and Methods: We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models. Results: After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02-3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1-141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants, was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004). Conclusion: This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1-141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.

Triptolide Inhibits Proliferation and Induces Apoptosis of Human Melanoma A375 Cells

Tao, Yue,Zhang, Meng-Li,Ma, Peng-Cheng,Sun, Jian-Fang,Zhou, Wu-Qing,Cao, Yu-Ping,Li, Ling-Jun Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Triptolide, a diterpenoid obtained from Tripteryglum wilfordii Hook.f, has attracted interest for its antitumor activities against human tumor cell lines in recent years. This report focuses on anti-proliferative and pro-apoptotic activities in human melanoma A375 cells assessed by CCK8 assay, Hoechst 33258 staining and flow cytometry. In addition, triptolide-induced arrest in the S phase was also observed. Caspase assays showed the apoptosis induced by triptolide was caspase-dependent and probably through intrinsic apoptotic pathways. Furthermore, expression of NF-${\kappa}B$ (p65) and its downstream factors such as Bcl-2, Bcl-$X_L$ was down-regulated. Taken together, the data indicate that triptolide inhibits A375 cells proliferation and induces apoptosis by a caspase-dependent pathway and through a NF-${\kappa}B$-mediated mechanism.

Effects of N-acetylcysteine on the energy status and antioxidant capacity in heart and liver of cold-stressed broilers

Li Chengcheng,Peng Meng,Liao Man,Guo Shuangshuang,Hou Yongqing,Ding Binying,Wu Tao,Yi Dan 아세아·태평양축산학회 2020 Animal Bioscience Vol.33 No.9

Objective: Cold stress induces oxidative damage and impairs energy status of broilers. N-acetylcysteine (NAC) exhibits antioxidant properties and modulates energy metabolism of animals. This study was conducted to investigate the effects of NAC on energy status and antioxidant capacity of heart and liver in the cold-stressed broilers. Methods: The experiment consisted of 4 treatments in a 2×2 factorial arrangement with two diets (basal diet or plus 0.1% NAC) and two ambient temperatures (thermoneutral [conventional ambient temperature] or cold stress [10°C±1°C during days 15 to 42]). Results: No ascites were seen in cold-stressed broilers. NAC did not attenuate the impaired growth performance of stressed birds. However, NAC decreased plasma asparagine but increased aspartate levels in cold-stressed birds (p<0.05). NAC reduced hepatic adenosine triphosphate (ATP) but elevated adenosine diphosphate contents in unstressed birds (p< 0.05). The hepatic ratio of adenosine monophosphate (AMP) to ATP was increased in birds fed NAC (p<0.05). NAC decreased plasma malondialdehyde (MDA) level and cardiac total superoxide dismutase (T-SOD) activity in unstressed birds, but increased hepatic activities of T-SOD, catalase and glutathione peroxidase in stressed birds (p<0.05). NAC down-regulated hepatic AMP-activated protein kinase but up-regulated cardiac heme-oxigenase mRNA expression in stressed birds, and decreased expression of hepatic peroxisome proliferator-activated receptor coactivator-1α as well as hypoxia-inducible factor-1α in liver and heart of birds. Conclusion: Dietary NAC did not affect energy status but enhanced the hepatic antioxidant capacity by increasing the activities of antioxidant enzymes in cold-stressed broilers.

Synthesis and Characterization of pH-Responsive Poly(2-hydroxyethyl aspartamide)-g-Poly(β-amino ester) Graft Copolymer Micelles as Potential Drug Carriers

Tao Peng,Yi Li,안다운,김봉섭,이두성 한국고분자학회 2013 Macromolecular Research Vol.21 No.4

Novel pH-responsive graft copolymers consisting of poly(2-hydroxyethyl aspartamide)-g-poly(β-amino ester) (PHEA-g-PAE) were prepared from polysuccinimide, which is a thermal polycondensation product of aspartic acid, via the Michael-addition reaction with β-amino ester moieties. The chemical structures of the prepared graft copolymers were characterized by 1H NMR. Their micelle properties were examined by dynamic light scattering and fluorescence spectrometry. The transmission electron microscopy images demonstrated that these micelles were regularly spherical in shape. For cancer therapy, doxorubicin (DOX) was efficiently encapsulated into the micelles. The DOX loaded micelles exhibited relatively sharp pH-dependent DOX release behavior.

Preclinical Study of Cell Therapy for Osteonecrosis of the Femoral Head with Allogenic Peripheral Blood-Derived Mesenchymal Stem Cells

Tao Zhang,Qiang Fu,Ning-Ning Tang,Qian Zhang,Yi Liu,Jia-Chen Peng,Ning Fang,Li-Mei Yu,Jin-Wei Liu 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.4

Purpose: To explore the value of transplanting peripheral blood-derived mesenchymal stem cells from allogenic rabbits (rPBMSCs)to treat osteonecrosis of the femoral head (ONFH). Materials and Methods: rPBMSCs were separated/cultured from peripheral blood after granulocyte colony-stimulating factor mobilization. Afterwards, mobilized rPBMSCs from a second passage labeled with PKH26 were transplanted into rabbit ONFH models, which were established by liquid nitrogen freezing, to observe the effect of rPBMSCs on ONFH repair. Then, the mRNA expressions of BMP-2 and PPAR-γ in the femoral head were assessed by RT-PCR. Results: After mobilization, the cultured rPBMSCs expressed mesenchymal markers of CD90, CD44, CD29, and CD105, but failed to express CD45, CD14, and CD34. The colony forming efficiency of mobilized rPBMSCs ranged from 2.8 to 10.8 per million peripheralmononuclear cells. After local transplantation, survival of the engrafted cells reached at least 8 weeks. Therein, BMP-2 was up-regulated, while PPAR-γ mRNA was down-regulated. Additionally, bone density and bone trabeculae tended to increase gradually. Conclusion: We confirmed that local transplantation of rPBMSCs benefits ONFH treatment and that the beneficial effects are relatedto the up-regulation of BMP-2 expression and the down-regulation of PPAR-γ expression.